The Journal of Rheumatology
Volume 43, no. 5
Are the New ACR/EULAR Criteria the Ultimate Answer for Polymyalgia
Rheumatica Classification?
DARIO CAMELLINO and MARCO A. CIMMINO
J Rheumatol 2016;43;836-838
http://www.jrheum.org/content/43/5/836
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The Journal of Rheumatology is a monthly international serial edited by Earl D.
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Editorial
Are the New ACR/EULAR
Criteria the Ultimate Answer for
Polymyalgia Rheumatica
Classification?
Polymyalgia rheumatica (PMR) is a diagnostic limbo. If a
patient is evaluated by an experienced clinician who records
the usual set of signs and symptoms along with the pertinent
increased inflammatory markers, the diagnosis is usually
correct. However, in several instances, PMR may evolve or
transform into elderly onset rheumatoid arthritis (EORA), a
switch that cannot be easily predicted and is usually recognized only during followup1. When less experienced clinicians are involved, overdiagnosis and underdiagnosis of
PMR are relatively frequent because several conditions may
mimic the disease, and a gold standard for diagnosis confirmation is lacking.
The availability of the recent American College of
Rheumatology/European League Against Rheumatism
(ACR/EULAR) criteria is expected to improve PMR classification2. Clinicians may also be enticed to apply these
criteria in the individual patient although, as widely stated3,
criteria should be used for classification only. The multifaceted essence of PMR may account for the wide range of
its clinical presentations, making it difficult to identify a
1-size-fits-all set of criteria.
In this issue of The Journal, Ozen, et al4 describe a multicenter study dealing with the comparison of different sets of
PMR classification criteria, including the ACR/EULAR
criteria. The main findings of this study, which confirmed the
overall good performance of the criteria, are that they are not
optimal in differentiating PMR from seronegative
polyarthritis and that, if a cutoff for laboratory inflammation
is included, performance can increase. By comparing the
existing sets of criteria, several studies from the literature
obtained different results (Table 12,4,5,6,7,8,9). In Ozen’s study,
the new ACR/EULAR criteria showed a moderate-to-good
discriminating capacity between PMR and non-PMR.
However, the best performance was obtained by the Chuang,
et al criteria10, also in the case of differentiation between
PMR and EORA. In accordance with previous findings, the
Bird9, et al criteria showed the best sensitivity (94%), while
those of Jones and Hazleman11 and of Chuang, et al, showed
the highest specificity. The unexpected finding of Ozen’s
study is that the ACR/EULAR criteria showed more sensitivity than specificity, contrary to what was observed in the
original article2 and in Macchioni, et al6 (Table 1). In
addition, specificity of the ACR/EULAR criteria increased
when they were used to differentiate PMR from RA (but not
from its seronegative subset), again in disagreement with the
original study, which showed better performance when the
criteria were used to discriminate between PMR and noninflammatory shoulder diseases. This observation is surprising, because EORA is unanimously considered the most
challenging differential diagnosis.
Is PMR the same disease for all clinicians? It is ironic that
even if the same ingredients are used, the resulting cocktail
is so unpredictable. In fact, there is an overlap of 80% in the
different items of the 6 most frequently used criteria. In
particular, age over 50 years is considered in 4/6, elevated
erythrocyte sedimentation rate (ESR) or C-reactive protein
(CRP) in 6/6, morning stiffness in 4/6, bilateral shoulder pain
and stiffness in 6/6, and exclusion of other conditions,
especially peripheral arthritis in 5/6. However, the definition
of the single item is somewhat different. The nature of the
patients, control group population, and clinicians who apply
the criteria may further explain some of the discrepancies.
In the ACR/EULAR study2, the population studied was a
prospective cohort of new patients, whose diagnosis was
reevaluated after 6 months; the clinicians, who were from 21
centers in 10 countries, had considerable experience in the
disease and met several times to agree on diagnosis standardization; the control group were patients with conditions
mimicking PMR, including RA and noninflammatory
shoulder conditions. The single-center study by Macchioni,
et al6 was retrospective, patients were consecutively enrolled
and followed by expert clinicians, diagnosis was confirmed
at 12 months, and controls included mainly early RA and
various other rheumatic conditions. Ozen’s study4 was
See Validation of PMR classification criteria, page 893
836
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The Journal of Rheumatology 2016; 43:5; doi:10.3899/jrheum.160232
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Table 1. Performance of different sets of diagnostic/classification criteria. Values are expressed as percentages.
Sensitivity (%)
ACR/EULAR
ACR/EULAR US
Nobunaga
Jones and Hazleman
Healey
Chuang
Bird
Specificity (%)
ACR/EULAR
ACR/EULAR US
Nobunaga
Jones and Hazleman
Healey
Chuang
Bird
Ozen, et al4
Weigand, et al5
Macchioni, et al6
Dasgupta, et al2
89.5
91.3
73.7
47.4
48.1
80.5
94
85.2
81.5
92.6
92.6
58.2
63.1
80.3
77
89.2
68
66
57.7
52
83.1
93.7
89.4
88
50
83.3
66.7
40.7
87
81.5
91.3
97.8
96.7
81.5
81.5
40.2
78
81
Bird, et al7
Nobunaga, et al8
Bird, et al9
67.8
84.9
93.1
48
42.9
89.7
100
92
98.3
100
100
95
60.2
80
93.3
99.5
ACR/EULAR: American College of Rheumatology/European League Against Rheumatism; US: ultrasonography.
prospective and multicenter (18 centers), enrolled patients
showed the same features as the ACR/EULAR study, and
diagnosis was validated after 12 months. The rate of misclassification was similar; in the original ACR/EULAR study,
8% of patients moved from the PMR to the control cohort
and 4.7% of controls were reclassified as PMR by the end of
followup; and in Ozen’s study 8.3% of patients with PMR
changed diagnosis, with more than half reclassified as RA.
As a result, it is difficult to find rough methodological differences between these studies that could explain the different
results obtained. The only variables remaining are the
percentage mix of controls and the clinician’s ability to make
a diagnosis and perform ultrasonography (US).
Which Additional Aids Could Be Useful to Identify and
Support the Correct Diagnosis?
Ultrasonography. Is US the magic solution for this problem?
In the original study2, the addition of US increased specificity
from 78% to 81%, but US decreased sensitivity from 68% to
66%. In another study6, US highly increased specificity from
81.5% to 91.3%, and did not change sensitivity. Conversely,
Weigand, et al5 observed a decrease in sensitivity from 85.2%
to 81.5%. Ozen, et al4 found contrasting results, with an
increase in sensitivity from 89.5% to 91.3% and a decrease
in specificity from 57.7% to 52%. And in the same report,
US contributed best when used to differentiate PMR from
noninflammatory shoulder disorders. US may increase our
ability to classify PMR, but is probably not necessary for
diagnosis because its effect on sensitivity is minimal or
nonexistent. Other advanced imaging techniques, such as
contrast-enhanced magnetic resonance imaging and positron
emission tomography/computerized tomography, possibly
share the same problem12.
Inflammatory markers. The ACR/EULAR criteria require the
presence of abnormal ESR and/or CRP, considered as a
dichotomous variable. In their cohort, Ozen, et al found that
in establishing an ESR cutoff 2 times higher than the upper
normal value, the best performance of sensitivity and specificity was achieved. When a CRP increase of at least 2 times
was also set, specificity improved, but sensitivity slightly
decreased. The reason why the authors of the ACR/EULAR
criteria did not include CRP concentrations or ESR values in
their set of criteria was that blood tests were not centralized
or standardized. This was also the case for Ozen, et al’s work
and therefore their results, although theoretically sound,
should be considered with caution. In the majority of elderly
patients, however, mild degrees of systemic inflammation,
often due to atherosclerosis, should be taken into account13.
This situation could also justify why, in the cohort of Ozen,
et al, most patients with noninflammatory conditions of the
shoulders had elevated ESR (79%) or CRP (57%). What is
more, several reports have shown that up to 10% to 20% of
PMR patients present with normal inflammatory indices14.
As a result, if only those patients with an increase of ESR or
CRP are included in the PMR category, the correct diagnosis
could be missed in about 1 in 5. What is needed is another
prospective study where laboratory examinations are
centralized.
Response to glucocorticoids. For many years a good response
to glucocorticoid (GC) therapy has been used as a confirmatory criterion, an approach that could be misleading,
because other diseases, whether rheumatic or not, are
improved by GC. In addition, it is not clear how to define this
good response. The ACR/EULAR study reported it as over
75% global response to 15 to 20 mg/day of prednisone. This
result was not reached in 29% of patients at 4 weeks, which
is contrary to the common opinion that patients with PMR
always respond dramatically to GC. There was no association
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Editorial: Camellino & Cimmino
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837
between the scores obtained on either algorithm and the
response to GC at 4 and 26 weeks, which suggests that GC
response cannot be used as part of PMR classification.
Workup of patients. Another potential pitfall is the subjectivity of each physician in deciding on the diagnostic investigations for patients with suspected PMR. Standardization
of diagnostic procedures was another aim of the
ACR/EULAR criteria group, which involved a wide range of
participants, including patients and physicians (rheumatologists, internists, and general practitioners) to emphasize
different viewpoints. The 2015 recommendations for
management of PMR15 provide a list of mandatory laboratory
tests, which should be performed at baseline for all patients.
These include CRP and/or ESR, rheumatoid factor and/or
anticyclic citrullinated peptide antibodies, blood cell count,
glucose, creatinine concentration, liver function tests, bone
profile, and dipstick urinalysis. In addition, in selected
instances, additional tests such as protein electrophoresis,
thyroid stimulating hormone, creatine kinase, Vitamin D,
antinuclear antibodies, anti-neutrophil cytoplasmic antibodies, or tuberculin skin tests should be performed.
Adoption of these procedures should diminish diagnostic
variability among clinicians.
The ACR/EULAR criteria seem to constitute progress in
the classification of PMR, although more data are needed on
their prospective evaluation in different settings, with an eye
to standardizing the numerous variables at work.
DARIO CAMELLINO, MD;
MARCO A. CIMMINO, MD,
Research Laboratory and Academic Division of Clinical Rheumatology,
Department of Internal Medicine,
University of Genoa,
Genoa, Italy.
Address correspondence to Dr. D. Camellino, Research Laboratory and
Academic Division of Clinical Rheumatology, Department of Internal
Medicine, University of Genoa, Viale Benedetto XV, 6, 16132 Genoa,
Italy. E-mail: [email protected]
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J Rheumatol 2016;43:836-8; doi:10.3899/jrheum.160232
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The Journal of Rheumatology 2016; 43:5; doi:10.3899/jrheum.160232
Downloaded from www.jrheum.org on June 16, 2017 - Published by The Journal of
Rheumatology